Succinic acid (SA) is an organic chemical of major commercial potential. Although the current market for SA is limited by its comparatively high price, it has been proposed as a feedstock for a variety of high-volume commodity chemicals, including 1,4-butanediol (BDO), gamma-butyrolactone (GBL), maleic anhydride (MA), and tetrahydrofuran (THF), among others. The recent description of biodegradable polypropylene succinate in the form of a stereocomplex with properties comparable to LDPE may also stimulate new commercial applications. SA is conventionally sourced via the C4 stream of the light naphtha raffinate of petroleum, usually by hydrogenation of MA or maleic acid, or oxidation of BDO, although there are other approaches. Recently, however, a number of companies have begun producing SA via fermentative pathways with the goal of becoming competitive with petrochemical routes, such that the global demand for SA has been predicted to increase from the current <100 kT to >700 kT per annum by 2020, representing a ca. $1B market.
The biological route to succinic acid is centered around native overproduces bacteria and genetically engineered E. coli. Carbon sources are typically sugars, which may be derived from lignocellulose hydrolysates. Although generally good yields and productivity have been reported, challenges associated with downstream processing, including selectivity issues, the use of bases as neutralizing agents, and product isolation complicate the overall economics of the process.
In principle, chemical-catalytic pathways offer much faster and more scalable routes to SA from carbohydrates. Although no practical access to SA directly from raw biomass has yet been developed, approaches via furfural and levulinic acid, both one step removed from biomass, have been described. Thus, Choudhary et al. recently reported the oxidation of furfural, a derivative of hemicellulose, with H2O7 at 80° C. over 24 hours to give SA in up to 74% yield. However, the SA was contaminated with a maleic acid by-product and the reaction is dependent on an ultimately degradable catalyst (Amberlyst-15) (Chem. Lett 2012, 41, 409). Beyond this, the cost of the feedstock and long reaction period give little advantage over fermentative routes. Related methods involving furfural and other furans using a range of oxidants and catalysts generally give SA in lower yields and selectivities, and are described in reviews.
Levulinic acid (LA) is a renewable feedstock of exceptional promise. Unlike furfural, LA can be derived both from hemicellulose and the major, cellulosic fraction of carbohydrates. It can be produced in high yield via the acidic processing of biomass, and although this is practiced commercially only on a limited scale at present, economic projections have indicated that the production costs of LA could fall as low as $0.04-$0.10/lb. LA can also be accessed in high yield by the hydrolysis of the biomass derived platform molecule 5-(chloromethyl)furfural (CMF). As such, the potential of LA to unlock key renewable markets is vast.
The conversion of LA to SA was first described in a paper by Tollens as early as 1879. Nitric acid was employed as the oxidant, resulting in a mixture of organic acids, including SA, albeit in low yield (Chem. Ber. 1879, 12, 334). The first report of the action of hydrogen peroxide on LA was published in 1934, which described a reaction at 60° C. in the presence of a cupric salt catalyst, again giving a mixture of carboxylic acids but only trace SA (Biochem. J. 1934, 28, 892). U.S. Pat. No. 2,676,186 reported the gas phase oxidation of LA with O2 and a vanadium catalyst at 375° C., wherein a maximum yield of 83% was claimed. This approach might have been of preparative interest were not the conditions so severe.
The current emphasis on green chemical production has led to a renewed interest in the conversion of LA to SA, and a flurry of recent publications describing this reaction has appeared. Thus, WO 2012/044168 describes the heating of LA with nitric acid-NaNO2 at 40° C. for 4 h to give mixtures of SA and oxalic acid, the former in up to 52% yield. Liu et al. reported the application of a Mn(ITT) catalyst in the oxidation of methyl levulinate at 90° C. under 5 bar of O2 to give a mixture of dimethyl succinate, malonate, and oxalate esters, along with related acetal derivatives (ChemSusChem 2013, 6, 2255). The maximum yield of succinate was 52% in a 20 hour reaction. Podolean et al. employed Ru(III) functionalized silica-coated magnetic nanoparticles under 10 bar O2 at 150° C. for 6 hours in the conversion of LA to SA, where catalyst recycling experiments demonstrated good reusability (×3) at conversions of 54-58% and a 4% loading of ruthenium (Green Chem. 2013, 15, 3077). Finally, an interesting reaction was reported by Caretto and Perosa that involved simple heating of LA in a dimethylcarbonate/base mixture at 200° C. for 4 h to give dimethyl succinate among a range of other products in up to 20% yield (Sustainable Chem. Eng. 2013, 1, 989).
What is needed is a process that overcomes the modest yields, poor selectivity, severe conditions, and/or potentially foulable catalysts in the prior processes. Surprisingly, the present invention meets this and other needs.
3-Hydroxypropanoic acid (HPA) is considered a renewable target molecule of enormous latent potential, due to the fact that it provides a direct entry into the vast market for acrylic acid and its derivatives, while at the same time unlocking the bio-compatible/degradable HPA homopolymer market, which also shows much promise. The production of HPA from biomass sources is described in the literature almost exclusively by means of fermentation of glucose or glycerol. Although advances have been made, particularly in the development of recombinant yeast as producers, a number of technical hurdles remain, particularly associated with performance and downstream processing. HPA can also be produced via petrochemical approaches which have generally involved the hydration of acrylic acid or oxidation of allylic alcohol or propanediol, but current initiatives place a greater premium on the production of chemical drop-ins from renewable resources, rather than making biochemicals from petroleum.
In principle, chemical-catalytic pathways offer much faster and more scalable routes to HPA from carbohydrates than fermentative approaches, and a straightforward opportunity for the production of HPA from biomass appeared to present itself in the selective oxidation of levulinic acid (LA). We reasoned that if the selectivity of the oxidation of LA to SA with hydrogen peroxide could be reversed to favor the alternative migration product, a complementary route to HPA would also be forthcoming. Surprisingly, the present invention provides the analogous conversion of LA into HPA using H2O2 under modified reaction conditions.